Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review.

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Astaxanthin counteracts the effects of heat shock on the maturation of bovine oocytes.

The cellular mechanisms induced by elevated temperature on oocytes are not fully understood. However, there is evidence that some of the deleterious effects of heat shock are mediated by a heat-induced increase in reactive oxygen species (ROS). In this context, carotenoid antioxidants might have a thermoprotective effect. Therefore, the objective of this study was to determine the role of astaxanthin (AST) on oocyte ROS production and on the redox profile and developmental competency of cumulus-oocyte complexes (COCs) after 14h heat shock (41°C) during in vitro maturation (IVM). Exposure of oocytes to heat shock during IVM increased ROS and reduced the ability of the oocyte to cleave and develop to the blastocyst stage. However, 12.5 and 25nM astaxanthin rescued these negative effects of heat shock; astaxanthin counteracted the heat shock-induced increase in ROS and restored oocyte developmental competency. There was no effect of astaxanthin on maturation medium lipid peroxidation or on glutathione peroxidase and catalase activity in oocytes and cumulus cells. However, astaxanthin stimulated superoxide dismutase (SOD) activity in heat-shocked cumulus cells. In conclusion, direct heat shock reduced oocyte competence, which was restored by astaxanthin, possibly through regulation of ROS and SOD activity in oocytes and COCs.

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Effect of strontium ranelate on pain behavior in an experimental model of osteoarthritis.

Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects of decreasing the risk of fractures and an indication of reducing the progression of osteoarthritis (OA). This study aimed to investigate the effects of SrRan as either a prophylactic or a treatment drug, using an OA rat model to assess pain behavior. A monoiodoacetate (MIA)-induced knee joint OA model in Wistar rats was used. Thirty Wistar rats (both sexes, 60 days old) were distributed in five groups of 6 rats each: the control group, that received no intervention; a prophylactic group, that received oral administration of 25 mg·kg-1·day-1 of SrRan for 28 days before induction of OA; a group treated with 25 mg·kg-1·day-1 of SrRan for 28 days after OA induction; a group treated with 50 mg·kg-1·day-1 during 28 days after OA induction; and a group that received oral saline for 28 days after induction. The assessment of pain behavior was performed considering articular incapacitation (weight-bearing test), mechanical hyperalgesia (Randall Selitto test) and motor activity (rotarod test), on days 0, 7, 14, 21, and 28. This experiment did not yield a significant difference when comparing the group that received SrRan prophylactically with the groups treated with 25 or 50 mg·kg-1·day-1 and the group that received oral saline. Thus, SrRan did not provide analgesia in either treated rats or as a prophylactic drug with the tested doses. Higher doses should be tested further to achieve possible significant results.

[Vascular reconstruction for limb preservation during sarcoma surgery: a case series and a management algorithm]. / Reconstrucción vascular durante la cirugía de sarcomas para la preservación de extremidades: serie de casos y algoritmo de manejo.

OBJECTIVE: To evaluate the results of vascular reconstruction in soft tissue sarcoma surgery and establish an algorithm based on current evidence. MATERIAL AND METHODS: We studied patients undergoing soft-tissue sarcoma in a tertiary hospital. A retrospective review of 8 cases was carried out, analysing the demographics, surgical planning, complications, disease-free survival and bypass patency. RESULTS: Successful limb preservation was observed in all patients, and the bypass remained patent in all cases. The mean follow-up was 38.4 months average, with 87.5% survival and no recurrences. CONCLUSIONS: The involvement of major vascular structures in soft tissue sarcomas of the limbs does not necessarily exclude resectability. In selected cases, resection is possible with vascular reconstruction and limb preservation. However, multidisciplinary planning is needed.

Indications of microsurgery in soft tissue sarcomas.

UNLABELLED: Sarcomas are uncommon tumors and free-margin surgical resection remains the single most important treatment in the curative therapy of soft tissue sarcomas. Refinements in surgical techniques have led to increased function preservation and limb salvage. PATIENTS AND METHODS: The records of patients (n = 41) who underwent microsurgical soft tissue reconstruction subsequent to resection of soft tissue sarcoma during the period 1998 to 2010 were reviewed and compared with a general nonmicrosurgery group (n = 188) in relation to clinicopathological characteristics, surgical procedures, postoperative complications, time until start of adjuvant radiation, functional outcome (Toronto Extremity Salvage Score, TESS), local recurrence, free survival, and disease-specific survival. RESULTS: Forty-one patients (age range: 23 to 95 years) received a total of 42 free flaps. When compared with the general nonmicrosurgery group, these patients presented significant differences with regard to location, histological grade, and neoadjuvant treatments. Complications were encountered in 10 cases, including 3 patients with complete flap loss and 1 patient with partial flap loss; other complications were cervical fistulae, knee arthritis, nonconsolidation, and wound infection. Extremity salvage was achieved in 90% (19/21) of limb sarcomas, with these patients showing adequate postoperative ambulation (TESS 77 ± 16) and adequate use of the upper extremity (TESS 66 ± 26). Two patients underwent amputation after recurrence. Disease-specific survival rates at 5 and 10 years were 79.49% and 76.93%, respectively. CONCLUSION: The microsurgical repair of sarcoma defects is a reliable option that, though not free of complications, is necessary in selected cases such as patients receiving neoadjuvant treatments and those with head and neck location and high-grade tumors. The procedure enables both adequate oncosurgical resection and function preservation. Our microsurgical sarcoma reconstruction data, based on an observation period of 12 years and presenting the results of 42 free tissue transfers in 41 patients, adds further evidence to the previously published smaller series.

The peroxisomal protein import machinery--a case report of transient ubiquitination with a new flavor.

The peroxisomal protein import machinery displays remarkable properties. Be it its capacity to accept already folded proteins as substrates, its complex architecture or its energetics, almost every aspect of this machinery seems unique. The list of unusual properties is still growing as shown by the recent finding that one of its central components, Pex5p, is transiently monoubiquitinated at a cysteine residue. However, the data gathered in recent years also suggest that the peroxisomal import machinery is not that exclusive and similarities with p97/Cdc48-mediated processes and with multisubunit RING-E3 ligases are starting to emerge. Here, we discuss these data trying to distill the principles by which this complex machinery operates.